Inhibitory Potential of Apium graveolens L. Extract on Inflammation in Diethylnitrosamine-induced Hepatocellular Carcinoma in Mice

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with a recurrence rate of 80-90% and a high mortality rate. It is an inflammation-related cancer where cytokines production plays a major role, resulting in a non-resolving inflammation in the tumor microenvironment, which promotes the disease. Therefore, targeting inflammation is a logical way to combat HCC. Natural products can be helpful in the co-treatment and prevention of HCC. Hypothesis: This study aimed to evaluate the hepatoprotective properties of a methanolic extract of Apium graveolens L. (MAG) in diethylnitrosamine (DEN)-induced toxicity in BALB/c mice. Materials and Methods:We checked the antioxidant, anti-inflammatory, and anti-cancer properties of MAG. DEN is known to induce oxidative stress by increasing reactive oxygen species (ROS) production. This can result in liver damage, increased SGOT, SGPT, and ALP activity in serum, increased expression of HCC biomarkers like AFP and GPC-3, and increased levels of the inflammatory biomarkers NF-kappa B, IL-6, IL-4, IL-1 beta, and TNF-alpha. The above factors can cause the activation of the inflammatory signaling pathways, triggering the development of HCC. Results: MAG was able to lower the detrimental effects of DEN by restoring liver function; decrease oxidative stress by increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx), and gamma-L-glutamyl-L-Cysteinyl-glycine (GSH); decrease the inflammatory factors responsible for HCC; and increase caspase-3 activity. Molecular docking studies showed how phytoconstituents like luteolin, apigenin, and kaempferol present in MAG could potentially be responsible for lowering the effects of DEN in the mice's liver. Conclusion: Altogether, the present study showed that MAG was able to ameliorate inflammation in the DEN-induced liver carcinogenesis in BALB/c mice. To the best of the authors' knowledge, this is the first report on the use of a whole plant (Apium graveolens) in an anti-cancer study in a mouse model.